• Interstitial fibrosis [ Time Frame: Baseline biopsy ]
  Extent of interstitial fibrosis in kidney biopsy assessed using a semi-quantitative scale on light microscopy of biopsy sections
• Glomerulosclerosis [ Time Frame: Baseline biopsy ]
  Extent of glomerulosclerosis in kidney biopsy assessed using a semi-quantitative scale on light microscopy of biopsy sections
• Renal function change [ Time Frame: Baseline biopsy ]
  Slope of eGFR decline

• Interstitial fibrosis [ Time Frame: Baseline biopsy ]
  Degree of interstitial fibrosis in kidney biopsy
• Glomerulosclerosis [ Time Frame: Baseline biopsy ]
  Degree of glomerulosclerosis in kidney biopsy
• Renal function change [ Time Frame: Baseline biopsy ]
  Slope of eGFR decline

RESEARCH OBJECTIVES A. To identify differences in transcription profiles obtained from residual kidney tissue which was obtained for clinical purposes.

B. To identify differences in transcription profile between patients whose loss of kidney function progresses rapidly (eGFR decline ≥4ml/min/year) and in whom it progresses more slowly (eGFR decline <4ml/min/year).

C. To identify differences in transcription profile between predominantly glomerular and predominantly tubulointerstitial histopathological types .

D. To identify new pathogenetic pathways that may become targets for therapeutic intervention

METHODS The planned study centres on the use of archival biopsy material that is superfluous to what is or would be needed for clinical care (01/01/1995 to 31/05/2018 , n= approximately 400-500). Archived samples will be collected from St. Michael's Hospital and a number of collaborating centres, including but not limited to University of British Columbia, the University of Manitoba, and the University of Ottawa.

RNA will be extracted from the biopsy material using either the core that has been used for immunofluorescence microscopy and is stored at -80˚C, and/or the core that is formalin-fixed, embedded in paraffin wax and stored at room temperature. The RNA thereby extracted will be subjected to detailed interrogation by RNASeq to quantify the expression level of mRNAs (transcriptome) and compare differences, as indicated in the research objectives detailed above. The transcriptome will then be related to the clinical course (eGFR decline) and histopathological changes, in addition to examining potentially pathogenetically important and that are amenable to therapeutic intervention.

Histopathology will also be performed and classified according to established systems.

Clinical information that would be retrieved from patients' medical records are listed below.

Clinical data

1. Age
2. Gender
3. Ethnicity
4. Diabetes history
5. Diabetes type: 1, 2
6. Retinopathy history
7. Smoking history
8. Medications
9. Comorbidities
10. Past medical history
11. Primary nephrologist Laboratory data (prior to biopsy, at biopsy and post-biopsy)

12. Renal function measures and calculations. For example:

    i. Serum creatinine, eGFR ii. Change in creatinine and eGFR iii. Urinary albumin:creatinine values and ratio (ACR) iv. Urine protein:creatinine values and ratio (PCR) v. Urinary protein excretion rate (UPEx) vi. Changes in ACR, PCR, UPEx

13. Diabetes measures and calculations. Biopsy data
14. Biopsy related data

Each site will locally maintain a confidential Master Linking Log.

De-identified data will be entered into a secure REDCap database that is hosted by St. Michael's Hospital.

1. Cases: A group of patients with diabetic kidney disease
2. Controls: A group of healthy control patients

• Diabetic Nephropathies
• Kidney Disease, Chronic

• Diabetic kidney disease
  Patients with archived biopsies with a pathologic diagnosis of diabetic kidney disease, interstitial fibrosis/tubular atrophy, or nephrosclerosis.
  Intervention: Other: RNA sequencing
• Healthy controls
  Potential living donors with archived biopsies performed as part of their donor workup and with no diagnostic abnormalities
  Intervention: Other: RNA sequencing

Inclusion Criteria (diabetic kidney disease cases):

• history of type 1 or type 2 diabetes
• at least 1 archived native kidney biopsy that demonstrates either pure diabetic kidney disease or features of non-specific vascular disease, including glomerulosclerosis, non-inflammatory vascular disease,
• sufficient remaining archived kidney biopsy tissue for RNA sequencing (100 um thick tissue section) and histologic analysis (PAS and Masson Trichrome staining)

Exclusion Criteria (diabetic kidney disease cases):

• less than 3 eGFR values post-biopsy
• latest recorded eGFR values less than 6 months post-biopsy

Inclusion Criteria (healthy controls):

- at least 1 native kidney disease biopsy with no diagnostic abnormality

• University of Ottawa
• University of British Columbia
• University of Manitoba